(191cc) Development of NIR-II Nanoparticle Contrast Agents for Photoacoustic Imaging

Wang, L. Z., Princeton University
Lu, H. D., Princeton University
Fagan, M. R., Princeton University
Lim, T. L., Princeton University
Kudisch, B. J., Princeton University
Heinmiller, A., FUJIFILM VisualSonics
Prud'homme, R. K., Princeton University
Scholes, G. D., University of Toronto

Developing technologies for cancer treatment and diagnosis
is a vast yet very complex healthcare problem. New treatments are designed
every day for each specific case of tumors, but cancer diagnosis technology has
yet to keep up. This creates a situation where many treatments options are
available but physicians are unable to select the best course of action due to
limited information on tumor morphology. This lack of a fast, inexpensive, and
safe method to image cancers remains the current bottleneck for effective
therapies. The upcoming light-sound hybrid imaging modality, photoacoustic
imaging (PA), is already recognized for being able to produce high resolution
images without the need for expensive machinery and ionizing radiation. To
maximize imaging depth and reduce signal attenuation, there is a drive to
develop photoacoustic contrast agents that absorb in the Near Infrared II
(900-2000nm) ranges. We here present the development of stable NIR-II active
nanoparticles (NPs), utilizing the controlled self-assembly mechanism, Flash
Nanoprecipitation (FNP). After screening potential NIR-II dyes, 10 distinct
dye-encapsulated NPs were developed with sizes ranging from 20 to 180nm. These
results shed light on the molecular requirements for nanoencapsulation into
stable particles. NP sizes could be precisely tuned with co-core material,
whereas the absorbance profiles remained constant. Thus, the addition of
co-core material can be used to tune bulk properties and nanoparticle
accumulation via EPR to tumors or clearance through the liver and spleen, while
keeping the imaging properties constant. When kept frozen and in the dark,
NIR-II dye NPs were determined to be stable for up to 7 days, and are thus
suitable for long-term storage and use. While there was slight blue-shifts in
the dyes’ absorbance due to H-stacking after encapsulation, these particles
exhibited strong NIR-II photoacoustic activity in the 1200-1300 nm region,
where water and background signals are negligible. These particles represent the
first successful incorporation of NIR-II active organic dye into NPs as
contrast agents for PA imaging.